Interleukin-6 signaling pathway in targeted therapy for cancer

Cancer Treatment Reviews

Volumn 38, Issue 7, 2012, Pages 904-910

  Guo, Yuqi ^a,b   Xu, Feng ^c   Lu, Tianjian ^c   Duan, Zhenfeng ^b   Zhang, Zhan ^a,b  

^a ZHENGZHOU UNIVERSITY   (China)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

Cancer; Interleukin 6; Monoclonal antibodies; Stat3; Targeted therapy

Indexed keywords

ABAGOVOMAB; BORTEZOMIB; CLAZAKIZUMAB; CORTICOSTEROID; DEXAMETHASONE; ESTROGEN; INTERLEUKIN 6; INTERLEUKIN 6 ANTIBODY; JANUS KINASE INHIBITOR; MONOCLONAL ANTIBODY; NONSTEROID ANTIINFLAMMATORY AGENT; PACLITAXEL; SILTUXIMAB; SIRUKUMAB; STAT3 PROTEIN; TOCILIZUMAB;

ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA; ANGIOGENESIS; APOPTOSIS; ARTHRITIS; BREAST CANCER; CANCER CELL; CANCER INHIBITION; CANCER PROGNOSIS; CANCER SURVIVAL; COLORECTAL CANCER; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; MOLECULARLY TARGETED THERAPY; MULTIPLE MYELOMA; MYELOPROLIFERATIVE NEOPLASM; NEOPLASM; NONHUMAN; OVARY CANCER; PROSTATE CANCER; PROTEIN EXPRESSION; PSORIASIS; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH;

ANTIBODIES, MONOCLONAL; HUMANS; INTERLEUKIN-6; MOLECULAR TARGETED THERAPY; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84865422083     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.04.007     Document Type: Review

References (125)

1. Ara T., Declerck Y.A. Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 2010, 46:1223-1231.
2. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006, 8(Suppl. 2):S2.
3. Fielding C.A., McLoughlin R.M., McLeod L., Colmont C.S., Najdovska M., Grail D., et al. IL-6 regulates neutrophil trafficking during acute inflammation via STAT3. J Immunol 2008, 181:2189-2195.
4. Prieto J. Inflammation, HCC and sex: IL-6 in the centre of the triangle. J Hepatol 2008, 48:380-381.
5. Paul W. IL-6: a multifunctional regulator of immunity and inflammation. Jpn J Cancer Res 1991, 82:1458-1459.
6. Banks W.A., Kastin A.J., Gutierrez E.G. Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci lett 1994, 179:53-56.
7. Kastritis E., Charidimou A., Varkaris A., Dimopoulos M.A. Targeted therapies in multiple myeloma. Target Oncol 2009, 4:23-36.
8. Adachi Y., Yoshio-Hoshino N., Nishimoto N. The blockade of IL-6 signaling in rational drug design. Curr Pharm Des 2008, 14:1217-1224.
9. Fulciniti M., Hideshima T., Vermot-Desroches C., Pozzi S., Nanjappa P., Shen Z., et al. A high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma. Clin Cancer Res 2009, 15:7144-7152.
10. Shi Y., Frost P.J., Hoang B.Q., Benavides A., Sharma S., Gera J.F., et al. IL-6-induced stimulation of c-myc translation in multiple myeloma cells is mediated by myc internal ribosome entry site function and the RNA-binding protein, hnRNP A1. Cancer Res 2008, 68:10215-10222.
11. Lauta V.M. Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data. Cytokine 2001, 16:79-86.
12. Bellone S., Watts K., Cane S., Palmieri M., Cannon M.J., Burnett A., et al. High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer. Gynecol Oncol 2005, 98:92-98.
13. Songur N., Kuru B., Kalkan F., Ozdilekcan C., Cakmak H., Hizel N. Serum interleukin-6 levels correlate with malnutrition and survival in patients with advanced non-small cell lung cancer. Tumori 2004, 90:196-200.
14. Belluco C., Nitti D., Frantz M., Toppan P., Basso D., Plebani M., et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol 2000, 7:133-138.
15. Altundag O., Altundag K., Gunduz E. Interleukin-6 and C-reactive protein in metastatic renal cell carcinoma. J Clin Oncol 2005, 23:1044. author reply-5.
16. Negrier S., Perol D., Menetrier-Caux C., Escudier B., Pallardy M., Ravaud A., et al. Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6 - from the Groupe Francais d'Immunotherapie. J Clin Oncol 2004, 22:2371-2378.
17. Wei L.H., Kuo M.L., Chen C.A., Chou C.H., Lai K.B., Lee C.N., et al. Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway. Oncogene 2003, 22:1517-1527.
18. Garcia-Tunon I., Ricote M., Ruiz A., Fraile B., Paniagua R., Royuela M. IL-6, its receptors and its relationship with bcl-2 and bax proteins in infiltrating and in situ human breast carcinoma. Histopathology 2005, 47:82-89.
19. Salgado R., Junius S., Benoy I., Van Dam P., Vermeulen P., Van Marck E., et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer 2003, 103:642-646.
20. Zakrzewska I., Poznanski J. Changes of serum il-6 and CRP after chemotherapy in patients with ovarian carcinoma. Pol Merkur Lekarski 2001, 11:210-213.
21. Penson R.T., Kronish K., Duan Z., Feller A.J., Stark P., Cook S.E., et al. Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel. Int J Gynecol Cancer 2000, 10:33-41.
22. Culig Z., Steiner H., Bartsch G., Hobisch A. Interleukin-6 regulation of prostate cancer cell growth. J Cell Biochem 2005, 95:497-505.
23. Shinriki S., Jono H., Ota K., Ueda M., Kudo M., Ota T., et al. Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res 2009, 15:5426-5434.
24. Duan Z., Feller A.J., Penson R.T., Chabner B.A., Seiden M.V. Discovery of differentially expressed genes associated with paclitaxel resistance using cDNA array technology: analysis of interleukin (IL) 6, IL-8, and monocyte chemotactic protein 1 in the paclitaxel-resistant phenotype. Clin Cancer Res 1999, 5:3445-3453.
25. Duan Z., Lamendola D.E., Penson R.T., Kronish K.M., Seiden M.V. Overexpression of IL-6 but not IL-8 increases paclitaxel resistance of U-2OS human osteosarcoma cells. Cytokine 2002, 17:234-242.
26. Pu Y.S., Hour T.C., Chuang S.E., Cheng A.L., Lai M.K., Kuo M.L. Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in prostatic cancer cells. Prostate 2004, 60:120-129.
27. Wang Y., Niu X.L., Qu Y., Wu J., Zhu Y.Q., Sun W.J., et al. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett 2010, 295:110-123.
28. Trikha M., Corringham R., Klein B., Rossi J.F. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 2003, 9:4653-4665.
29. Hong D.S., Angelo L.S., Kurzrock R. Interleukin-6 and its receptor in cancer: implications for Translational Therapeutics. Cancer 2007, 110:1911-1928.
30. Chen Z., Malhotra P.S., Thomas G.R., Ondrey F.G., Duffey D.C., Smith C.W., et al. Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 1999, 5:1369-1379.
31. Puchalski T., Prabhakar U., Jiao Q., Berns B., Davis H.M. Pharmacokinetic and pharmacodynamic modeling of an anti-interleukin-6 chimeric monoclonal antibody (siltuximab) in patients with metastatic renal cell carcinoma. Clin Cancer Res 2010, 16:1652-1661.
32. Heinrich P.C., Behrmann I., Haan S., Hermanns H.M., Muller-Newen G., Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003, 374:1-20.
33. Heinrich P.C., Behrmann I., Muller-Newen G., Schaper F., Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 1998, 334(Pt 2):297-314.
34. Lauta V.M. A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and therapeutic implications. Cancer 2003, 97:2440-2452.
35. Scheller J., Ohnesorge N., Rose-John S. Interleukin-6 trans-signalling in chronic inflammation and cancer. Scand J Immunol 2006, 63:321-329.
36. Imada K., Leonard W.J. The Jak-STAT pathway. Mol Immunol 2000, 37:1-11.
37. Calo V., Migliavacca M., Bazan V., Macaluso M., Buscemi M., Gebbia N., et al. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol 2003, 197:157-168.
38. Levy D.E., Lee C.K. What does Stat3 do?. J Clin Invest 2002, 109:1143-1148.
39. Darnell J.E. STATs and gene regulation. Science 1997, 277:1630-1635.
40. Yu H., Jove R. The STATs of cancer - new molecular targets come of age. Nat Rev Cancer 2004, 4:97-105.
41. Leu C.M., Wong F.H., Chang C., Huang S.F., Hu C.P. Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene 2003, 22:7809-7818.
42. Ara T., Declerck Y.A. Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 2010, 46:1223-1231.
43. Jee S.H., Chu C.Y., Chiu H.C., Huang Y.L., Tsai W.L., Liao Y.H., et al. Interleukin-6 induced basic fibroblast growth factor-dependent angiogenesis in basal cell carcinoma cell line via JAK/STAT3 and PI3-kinase/Akt pathways. J Invest Dermatol 2004, 123:1169-1175.
44. Hsu J.H., Shi Y., Frost P., Yan H., Hoang B., Sharma S., et al. Interleukin-6 activates phosphoinositol-3' kinase in multiple myeloma tumor cells by signaling through RAS-dependent and, separately, through p85-dependent pathways. Oncogene 2004, 23:3368-3375.
45. Hov H., Tian E., Holien T., Holt R.U., Vatsveen T.K., Fagerli U.M., et al. C-Met signaling promotes IL-6-induced myeloma cell proliferation. Eur J of Haematol 2009, 82:277-287.
46. Scambia G., Testa U. Benedetti Panici P, Foti E, Martucci R, Gadducci A, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995, 71:354-356.
47. George D.J., Halabi S., Shepard T.F., Sanford B., Vogelzang N.J., Small E.J., et al. The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480. Clin Cancer Res 2005, 11:1815-1820.
48. Alexandrakis M.G., Passam F.H., Kyriakou D.S., Christophoridou A.V., Perisinakis K., Hatzivasili A., et al. Serum level of interleukin-16 in multiple myeloma patients and its relationship to disease activity. Am J Hematol 2004, 75:101-106.
49. Berek J.S., Chung C., Kaldi K., Watson J.M., Knox R.M., Martinez-Maza O. Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol 1991, 164:1038-1042. discussion 42-3.
50. Borsellino N., Belldegrun A., Bonavida B. Endogenous interleukin 6 is a resistance factor for cis-diamminedichloroplatinum and etoposide-mediated cytotoxicity of human prostate carcinoma cell lines. Cancer Res 1995, 55:4633-4639.
51. Conze D., Weiss L., Regen P.S., Bhushan A., Weaver D., Johnson P., et al. Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells. Cancer Res 2001, 61:8851-8858.
52. Cozen W., Gill P.S., Ingles S.A., Masood R., Martinez-Maza O., Cockburn M.G., et al. IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma. Blood 2004, 103:3216-3221.
53. Santer F.R., Malinowska K., Culig Z., Cavarretta I.T. Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells. Endocr-relat cancer 2010, 17:241-253.
54. Suchi K., Fujiwara H., Okamura S., Okamura H., Umehara S., Todo M., et al. Overexpression of Interleukin-6 suppresses cisplatin-induced cytotoxicity in esophageal squamous cell carcinoma cells. Anticancer Res 2011, 31:67-75.
55. Keller E.T., Wanagat J., Ershler W.B. Molecular and cellular biology of interleukin-6 and its receptor. Front Biosci 1996, 1:d340-d357.
56. Akira S., Taga T., Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol 1993, 54:1-78.
57. Nilsson M.B., Langley R.R., Fidler I.J. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 2005, 65:10794-10800.
58. Saidi A., Hagedorn M., Allain N., Verpelli C., Sala C., Bello L., et al. Combined targeting of interleukin-6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness. Int j cancer J Int du cancer 2009, 125:1054-1064.
59. Brozek W., Bises G., Girsch T., Cross H.S., Kaiser H.E., Peterlik M. Differentiation-dependent expression and mitogenic action of interleukin-6 in human colon carcinoma cells: relevance for tumour progression. Eur J Cancer 2005, 41:2347-2354.
60. Yao J.S., Zhai W., Young W.L., Yang G.Y. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: the role for KDR and MMP-9. Biochem Biophys Res Commun 2006, 342:1396-1404.
61. Fassone L., Gaidano G., Ariatti C., Vivenza D., Capello D., Gloghini A., et al. The role of cytokines in the pathogenesis and management of AIDS-related lymphomas. Leuk Lymphoma 2000, 38:481-488.
62. Sun R., Jaruga B., Kulkarni S., Sun H., Gao B. IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: regulation by SOCS3. Biochem Biophys Res Commun 2005, 338:1943-1949.
63. Grant S.L., Hammacher A., Douglas A.M., Goss G.A., Mansfield R.K., Heath J.K., et al. An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells. Oncogene 2002, 21:460-474.
64. Badache A., Hynes N.E. Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. Cancer Res 2001, 61:383-391.
65. Wang Y.D., De Vos J., Jourdan M., Couderc G., Lu Z.-Y., Rossi J.-F., et al. Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in promoting the growth of human myeloma cells. Oncogene 2002, 21:2584-2592.
66. Dankbar B., Padro T., Leo R., Feldmann B., Kropff M., Mesters R.M., et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood 2000, 95:2630-2636.
67. Schafer Z.T., Brugge J.S. IL-6 involvement in epithelial cancers. J Clin Invest 2007, 117:3660-3663.
68. Sansone P., Storci G., Tavolari S., Guarnieri T., Giovannini C., Taffurelli M., et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007, 117:3988-4002.
69. Sherry M.M., Reeves A., Wu J.K., Cochran B.H. STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem cells 2009, 27:2383-2392.
70. Rosen D.G., Mercado-Uribe I., Yang G., Bast R.C., Amin H.M., Lai R., et al. The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis. Cancer 2006, 107:2730-2740.
71. Huang M., Page C., Reynolds R.K., Lin J. Constitutive activation of stat 3 oncogene product in human ovarian carcinoma cells. Gynecol Oncol 2000, 79:67-73.
72. Gao S.P., Mark K.G., Leslie K., Pao W., Motoi N., Gerald W.L., et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest 2007, 117:3846-3856.
73. Quesnelle K.M., Boehm A.L., Grandis J.R. STAT-mediated EGFR signaling in cancer. J Cellular Biochem 2007, 102:311-319.
74. Grivennikov S., Karin M. Autocrine IL-6 signaling: a key event in tumorigenesis?. Cancer Cell 2008, 13:7-9.
75. Okamoto M., Kawamata H., Kawai K., Oyasu R. Enhancement of transformation in vitro of a nontumorigenic rat urothelial cell line by interleukin 6. Cancer Res 1995, 55:4581-4585.
76. Okamoto M., Oyasu R. Effect of transfected interleukin-6 in non-tumorigenic and tumorigenic rat urothelial cell lines. Int J Cancer J Int du cancer 1996, 68:616-621.
77. Eliopoulos A.G., Stack M., Dawson C.W., Kaye K.M., Hodgkin L., Sihota S., et al. Epstein-Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF-kappaB pathway involving TNF receptor-associated factors. Oncogene 1997, 14:2899-2916.
78. Leslie K., Gao S.P., Berishaj M., Podsypanina K., Ho H., Ivashkiv L., et al. Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation. Breast cancer research: BCR 2010, 12:R80.
79. Hartman Z.C., Yang X.Y., Glass O., Lei G., Osada T., Dave S.S., et al. HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis. Cancer Res 2011, 71:4380-4391.
80. Foran E., Garrity-Park M.M., Mureau C., Newell J., Smyrk T.C., Limburg P.J., et al. Upregulation of DNA methyltransferase-mediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6. Molecular cancer research: MCR 2010, 8:471-481.
81. Rojas A., Liu G., Coleman I., Nelson P.S., Zhang M., Dash R., et al. IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR. Oncogene 2011, 30:2345-2355.
82. Qiu Y., Ravi L., Kung H.J. Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 1998, 393:83-85.
83. Rutsch S., Neppalli V.T., Shin D.M., DuBois W., Morse H.C., Goldschmidt H., et al. IL-6 and MYC collaborate in plasma cell tumor formation in mice. Blood 2010, 115:1746-1754.
84. Ishikawa H., Tsuyama N., Liu S., Abroun S., Li F.J., Otsuyama K., et al. Accelerated proliferation of myeloma cells by interleukin-6 cooperating with fibroblast growth factor receptor 3-mediated signals. Oncogene 2005, 24:6328-6332.
85. Mizutani Y., Bonavida B., Koishihara Y., Akamatsu K., Ohsugi Y., Yoshida O. Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum(II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody. Cancer Res 1995, 55:590-596.
86. Duan Z., Foster R., Bell D., Mahoney J., Wolak K., Vaidya A., et al. Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 2006, 12.
87. Varterasian M.L. Advances in the biology and treatment of multiple myeloma. Curr Opin Oncol 1999, 11:3-8.
88. Mantovani G., Maccio A., Lai P., Ghiani M., Turnu E., Del Giacco G.S. Membrane-bound/soluble IL-2 receptor (IL-2R) and levels of IL-1 alpha, IL-2, and IL-6 in the serum and in the PBMC culture supernatants from 17 patients with hematological malignancies. Cell Biophys 1995, 27:1-14.
89. Voorhees P.M., Chen Q., Kuhn D.J., Small G.W., Hunsucker S.A., Strader J.S., et al. Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma. Clin Cancer Res 2007, 13:6469-6478.
90. Voorhees P.M., Chen Q., Small G.W., Kuhn D.J., Hunsucker S.A., Nemeth J.A., et al. Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. Br J Haematol 2009, 145:481-490.
91. Tomillero A., Moral M.A. Gateways to clinical trials. Methods Find Exp Clin Pharmacol 2009, 31:47-57.
92. Cavarretta I.T., Neuwirt H., Untergasser G., Moser P.L., Zaki M.H., Steiner H., et al. The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1. Oncogene 2007, 26:2822-2832.
93. Wallner L., Dai J., Escara-Wilke J., Zhang J., Yao Z., Lu Y., et al. Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice. Cancer Res 2006, 66:3087-3095.
94. Savino R., Ciapponi L., Lahm A., Demartis A., Cabibbo A., Toniatti C., et al. Rational design of a receptor super-antagonist of human interleukin-6. EMBO J 1994, 13:5863-5870.
95. Sato K., Tsuchiya M., Saldanha J., Koishihara Y., Ohsugi Y., Kishimoto T., et al. Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth. Cancer Res 1993, 53:851-856.
96. Mihara M., Kasutani K., Okazaki M., Nakamura A., Kawai S., Sugimoto M., et al. Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol 2005, 5:1731-1740.
97. Kaminska J., Nowacki M.P., Kowalska M., Rysinska A., Chwalinski M., Fuksiewicz M., et al. Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I-an independent prognostic factor. Tumour Biol 2005, 26:186-194.
98. Esfandi F., Mohammadzadeh Ghobadloo S., Basati G. Interleukin-6 level in patients with colorectal cancer. Cancer Lett 2006, 244:76-78.
99. Nikiteas N.I., Tzanakis N., Gazouli M., Rallis G., Daniilidis K., Theodoropoulos G., et al. Serum IL-6, TNFalpha and CRP levels in Greek colorectal cancer patients: prognostic implications. World J Gastroenterol 2005, 11:1639-1643.
100. Okada S., Okusaka T., Ishii H., Kyogoku A., Yoshimori M., Kajimura N., et al. Elevated serum interleukin-6 levels in patients with pancreatic cancer. Jpn J Clin Oncol 1998, 28:12-15.
101. Plante M., Rubin S.C., Wong G.Y., Federici M.G., Finstad C.L., Gastl G.A. Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer 1994, 73:1882-1888.
102. Zhang G.J., Adachi I. Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res 1999, 19:1427-1432.
103. Guo Y., Nemeth J., O'Brien C., Susa M., Liu X., Zhang Z., et al. Effects of siltuximab on the IL-6-induced signaling pathway in ovarian cancer. Clin Cancer Res 2010, 16:5759-5769.
104. Ashizawa T., Okada R., Suzuki Y., Takagi M., Yamazaki T., Sumi T., et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer 2005, 8:124-131.
105. Huang S.P., Wu M.S., Shun C.T., Wang H.P., Lin M.T., Kuo M.L., et al. Interleukin-6 increases vascular endothelial growth factor and angiogenesis in gastric carcinoma. J Biomed Sci 2004, 11:517-527.
106. Wu C.W., Wang S.R., Chao M.F., Wu T.C., Lui W.Y. K, et al. Serum interleukin-6 levels reflect disease status of gastric cancer. Am J Gastroenterol 1996, 91:1417-1422.
107. Moreau P., Harousseau J.L., Wijdenes J., Morineau N., Milpied N., Bataille R. A combination of anti-interleukin 6 murine monoclonal antibody with dexamethasone and high-dose melphalan induces high complete response rates in advanced multiple myeloma. Br J Haematol 2000, 109:661-664.
108. Ahmed B., Tschen J.A., Cohen P.R., Zaki M.H., Rady P.L., Tyring S.K., et al. Cutaneous castleman's disease responds to anti interleukin-6 treatment. Mol Cancer Ther 2007, 6:2386-2390.
109. Nishimoto N. Interleukin-6 as a therapeutic target in candidate inflammatory diseases. Clin Pharmacol Ther 2010, 87:483-487.
110. Coward J., Kulbe H., Chakravarty P., Leader D., Vassileva V., Leinster D.A., et al. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res 2011, 17:6083-6096.
111. Rossi J.F., Negrier S., James N.D., Kocak I., Hawkins R., Davis H., et al. A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer. Br J Cancer 2010, 103:1154-1162.
112. Karkera J., Steiner H., Li W., Skradski V., Moser P.L., Riethdorf S., et al. The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study. Prostate 2011, 71:1455-1465.
113. Fizazi K., De Bono J.S., Flechon A., Heidenreich A., Voog E., Davis N.B., et al. Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer. Eur J Cancer 2012, 48:85-93.
114. Dorff T.B., Goldman B., Pinski J.K., Mack P.C., Lara P.N., Van Veldhuizen P.J., et al. Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res 2010, 16:3028-3034.
115. van Rhee F., Fayad L., Voorhees P., Furman R., Lonial S., Borghaei H., et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol: Official J Am Soc Clin Oncol 2010, 28:3701-3708.
116. Emilie D., Wijdenes J., Gisselbrecht C., Jarrousse B., Billaud E., Blay J.Y., et al. Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms. Blood 1994, 84:2472-2479.
117. Nishimoto N., Yoshizaki K., Miyasaka N., Yamamoto K., Kawai S., Takeuchi T., et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2004, 50:1761-1769.
118. Mihara M., Nishimoto N., Ohsugi Y. The therapy of autoimmune diseases by anti-interleukin-6 receptor antibody. Expert Opin Biol Ther 2005, 5:683-690.
119. Nilsson M.B., Langley R.R., Fidler I.J. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 2005, 65:10794-10800.
120. Yokota S., Imagawa T., Mori M., Miyamae T., Nishimoto N., Kishimoto T. Phase II trial of anti-IL-6 receptor antibody (MRA) for systemic-onset juvenile idiopathic arthritis. Autoimmunity Rev. 2004, 3:599-600.
121. Plante M., Rubin S.C., Wong G.Y., Federici M.G., Finstad C.L., Gastl G.A. Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer 1994, 73:1882-1888.
122. Mesa R.A. Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis. IDrugs: The Inves Drugs J. 2010, 13:394-403.
123. Dawson M.A., Curry J.E., Barber K., Beer P.A., Graham B., Lyons J.F., et al. AT9283, a potent inhibitor of the Aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders. Br J Haematol 2010, 150:46-57.
124. Pardanani A., Vannucchi A.M., Passamonti F., Cervantes F., Barbui T., Tefferi A. JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia: (Official J Leukemia Soc Am, Leukemia Res Fund, UK) 2011, 25:218-225.
125. William A.D., Lee A.C., Blanchard S., Poulsen A., Teo E.L., Nagaraj H., et al. Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1. 1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem 2011, 54:4638-4658.